HLA-H: Transcriptional Activity and HLA-E Mobilization
François Jordier, Delphine Gras, Maria De Grandis, Xavier Benoît D’Journo, P. Thomas, Pascal Chanez, Christophe Picard, Jacques Chiaroni, Julien Paganini, Julie Di Cristofaro
Abstract
Little attention is paid to pseudogenes from the highly polymorphic HLA genetic region. The pseudogene HLA-H is defined as a non-functional gene because it is deleted at different frequencies in humans and because it encodes a potentially non-functional truncated protein. However, different studies have shown HLA-H transcriptional activity. We formerly identified 13 novel HLA-H alleles, including the H*02:07 allele, which reaches 19.6% in East Asian populations, and encodes a full-length HLA protein. The aims of this study were to explore expression and possible function of the HLA-H molecule. HLA-H may act as a transmembrane molecule and/or indirectly via its signal peptide by mobilizing HLA-E to the cell surface. We analyzed HLA-H RNA expression in Peripheral Blood Mononuclear Cells (PBMC), Human Bronchial Epithelial Cells (HBEC) and available RNA sequencing data from lymphoblastoid cell lines, and looked to see whether HLA-E was mobilized at the cell surface by the HLA-H signal peptide. Our data confirmed that HLA-H is transcribed, at similar levels to HLA-G. We characterized a hemizygous effect in HLA-H expression and expression differed according to HLA-H alleles; most interestingly, HLA-H*02:07 allele had the highest level of mRNA expression. We showed that HLA-H signal peptide incubation mobilized HLA-E molecules at the cell surface of T-Lymphocytes, monocytes, B-Lymphocytes and primary epithelial cells. Our results suggest that HLA-H may be functional but raise many biological issues that need to be addressed.